EXCEEDTHE SPACE PROVIDED. Elevated plasma levels of homocyst(e)ine [H(e)] are surprisingly common and strongly associated with endothelial dysfunction and a marked increase in vascular risk. Treatment with a combination of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12) reduces plasma H(e) levels in most cases, restores endothelial function, and regresses carotid plaque but there is no evidence that such treatmentwill reduce clinical events. The Vitamin Intervention for Stroke Prevention (VISP) study is adouble-masked, randomized, multi-center clinical trial designed to determine if, in addition to best medical/surgical management, high dose folic acid, vitamin B6, and B,2 supplements will reduce recurrent stroke compared to lower doses of these vitamins. Patients at least 35 years old with a non-disabling ischemic strokewithin 120 days, and screening plasma H(e)> the 25th percentile of benchmark population data are eligible. Secondary endpoints are myocardial infarction or fatal coronary heart disease. The study is designed to recruit 3600 patients (1800 in each treatment group) for 80% power for detection of a 30% treatment effect. Follow-up continues until recurrent stroke, death, or a maximum of two years. As of May 4, 2000, we have screened 4600 candidates for eligibility and have randomized 2395. We are blinded to the outcome of endpoints. Four hundred enrollees have completed the two-year followup. The followup rate is 94%. There have been no insurmountable impediments to implementaion of all the component parts of this study. A supplemental research proposal for use of frozen plasma samples of our cohart for genetic and coogulation studies is in preparation.